This is an application for a Mentored Clinical Scientist Development Award (K08) entitled "Identification and Functional Analysis of Renal Stem Cells." The candidate holds MD and PhD degrees, has completed a residency in Internal Medicine and a fellowship in Nephrology. During this award, the candidate will acquire the background and laboratory skills required to further develop as a clinical scientist in the areas of renal disease and kidney development. The goals of the proposal are: (1) To identify a specific cell marker that is unique to label retaining cells in the kidney papilla and can be used to enrich and track this population;(2) To delineate the function of kidney label retaining cells in vivo before and after injury;and (3) To identify and delineate the function of regulatory molecules in kidney label retaining cells that mediate injury in acute tubular necrosis and obstructive nephropathy. The proposed studies utilize techniques in tissue culture, microscopy, molecular and cell biology, and this program of research and study will strengthen and advance the training of the candidate in these areas. The candidate proposes an integrated program of study and research directed toward improved understanding of reparative processes and, more specifically, the response of renal progenitor cells to injury. Indeed, an ever-increasing number of investigations demonstrate that tissue regeneration occurs throughout adult life, often in organ systems thought to be irreparable. Such studies point to the post-injury restoration of biological structure and function via cell-replacement strategies. The need for a deep understanding of stem cell behavior is central to confronting these issues. Relevance of this proposal to public health: the prevalence of acute renal failure in the hospitalized setting remains high and multiplies in the setting of increased co-morbid conditions. Moreover, diseases initially involving the renal papilla such as analgesic nephropathy and sickle cell anemia often lead to more global renal injury and can lead to end stage renal disease. Only by understanding the molecular signaling that underlies the "sensing" of renal injury as well as the initiation of repair, will we be able to initiate application of this new methodology to long-standing medical problems in nephrology.